The A350 has been closed in both directions between Chippenham and Melksham after a serious crash left one person with life-threatening injuries.
Emergency services were called to the collision just north of Beanacre, near Lacock, at around 3pm on Tuesday.
The incident is believed to involve a single vehicle.
One person has suffered life-threatening injuries and is receiving emergency treatment from the Wiltshire and Bath Air Ambulance critical care team, supported by local ambulance crews.
A350 closed in both directions
Wiltshire Police has imposed a full closure of the A350 between Lackham Roundabout near Chippenham and Leekes Roundabout in Melksham.
Motorists have been warned that the major route is expected to remain shut for a considerable period and should find alternative routes.
A Wiltshire Police spokesperson said:
“Please be aware we are currently attending a serious collision on the A350 just north of Beanacre.
“We have put a full closure in place between Leekes Roundabout and Lackham Roundabout near Chippenham.
“The road is likely to be closed for the foreseeable future. Please find alternate routes.”
Air ambulance critical care team at scene
The Wiltshire and Bath Air Ambulance critical care team is treating the seriously injured casualty alongside other emergency crews.
Drivers are being urged to avoid the A350 through the affected area while emergency services continue working at the scene.
The closure is likely to cause significant disruption between Chippenham and Melksham.
There is currently no confirmed reopening time.
Further details about the circumstances surrounding the collision have not yet been released.